Oncotarget published "Down regulation of lactate dehydrogenase initiates apoptosis in HeLa and MCF-7 cancer cells through increased voltage-dependent anion channel protein and inhibition of BCL2" which reported that the authors have investigated the effect of inhibition of LDH-A on cells viability and identifying the mechanism of cell death in HeLa and MCF-7 cancer cells.
Human cervical cancer HeLa cell line and breast cancer MCF-7 cell line were used to investigate the effect of inhibition of LDH-A by sodium oxamate on cell survival and proliferation using western blot, spectrophotometry, and immunofluorescent study.
There was significant reduction in LDH-A and cell viability in a dose-dependent mode in both HeLa and MCF-7 SO-treated cancer cells.
While, the anti-apoptotic protein Bcl2 was significantly decreased in association with decreased LDH-A.
The Oncotarget authors conclude that Inhibition of LDH-A can decrease cells viability through activation of intrinsic apoptotic pathway via increased VDAC protein and inhibition of Bcl2 as well as activation of the extrinsic apoptotic pathway through activation of caspase-8.
The Oncotarget authors conclude that Inhibition of LDH-A can decrease cells viability through activation of intrinsic apoptotic pathway via increased VDAC protein
Dr. Suhail Al-Salam from The United Arab Emirates University said, "Malignant cells commonly use aerobic glycolysis for ATP production; this is known as the Warburg effect."
Furthermore, relevant studies have demonstrated that inhibition of LDH-A induces oxidative stress and suppresses tumor growth in a variety of cancer cell lines.
Since aerobic glycolysis is the favored way of ATP production in cancer cells, it becomes a very attractive target for cancer therapies.
Figure 12: (A) Showing high cytoplasmic expression of p-NFKB by non-treated MCF-7 cells (arrow). (B) Showing lower cytoplasmic expression of p-NFKB by SO 60 mmol treated MCF-7 cells (arrow). (C) Showing higher cytoplasmic expression of VEGF (arrowhead) and nuclear expression of BMI-1 (thin arrow) by non-treated MCF-7 cells. (D) Showing lower cytoplasmic expression of VEGF (arrowhead) and nuclear expression of BMI-1 (thin arrow) by SO 60 mmol treated MCF-7 cells. (E) Showing higher number of cells expressing ki-67 in non-treated MCF-7 cells (arrow). (F) Showing lower number of cells expressing ki-67 in SO 60 mmol treated MCF-7 cells (arrow).
Sodium oxamate is a competitive inhibitor of LDH-A, hence, the authors use SO to block aerobic glycolysis and reduce the main energy source in cancer cells.
Changes in apoptotic and oxidative stress pathways in association with the use of sodium oxamate in cervical and breast cancer cell lines aiming in identifying mechanism of cancer cell death following SO treatment are focused on in this study.
The Al-Salam Research Team concluded in their Oncotarget Research Output, "the Inhibition of LDH-A can decrease cells viability through activation of intrinsic apoptotic pathway via increased VDAC protein and inhibition of Bcl2 as well as activation of the extrinsic apoptotic pathway through activation of caspase-8."
DOI - https://doi.org/10.18632/oncotarget.27950
Full text - https://www.oncotarget.com/article/27950/text/
Correspondence to - Suhail Al-Salam - [email protected]
Keywords - cancer metabolism, LDHA, apoptosis, VDAC
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